Biomedical subjects
Publications and source records attributed to J D Murphy.
Readability of the Big Book used in Alcoholics Anonymous confirmed Mills' finding of an 8th- or 9th-grade reading level, but readability of the Small Book for Rational Recovery required college level reading.
Most of the methods of diagnostic angiography currently in use are well established, although newer methods such as intravascular ultrasound and Doppler measurement of coronary blood flow velocity have been introduced. This review concentrates on several recent developments in diagnostic catheterization, including the appropriate application of diagnostic catheterization and complications. Balloon coronary angioplasty, also a relatively mature technology, has reached the stage where its appropriate use, case selection, and outcomes are being scrutinized, as was reflected in the reports published last year. Its appropriate role in relation to coronary artery bypass surgery, and the continuing effort to solve the problem of restenosis are also reviewed.
OBJECTIVE: The purpose of this investigation was to determine the pharmacokinetic disposition of intravenous allopurinol and its metabolite oxypurinol in neonates with the hypoplastic left heart syndrome (HLHS) and to evaluate the subsequent degree of xanthine oxidase inhibition using serum uric acid as a marker. METHODS: Pharmacokinetic data were evaluated in 12 stable preoperative neonates with HLHS after a single intravenous allopurinol administration of 5 mg/kg or 10 mg/kg. Pharmacokinetic parameters were determined for elimination half-life, clearance, volume of distribution, and mean residence time. Xanthine oxidase inhibition, measured by serum uric acid reduction, was also measured. RESULTS: Pharmacokinetic parameters revealed no statistically significant differences between a 5-mg/kg and 10-mg/kg dose of intravenous allopurinol on elimination half-life, clearance, volume of distribution, and mean residence time. Mean serum uric acid levels were significantly reduced from baseline by 39.99 and 42.94%, respectively, in the 5- and 10-mg/kg treatment groups. DISCUSSION: The enzyme xanthine oxidase plays a key biochemical role in the generation of toxic oxygen-derived free radicals during ischemia-reperfusion conditions. Allopurinol and its active metabolite oxypurinol inhibit xanthine oxidase, and significantly reduce the conversion of hypoxanthine to xanthine and xanthine to uric acid. Cell injury may be caused by toxic oxygen free radicals produced by ischemia-reperfusion injury such as could occur during the repair of HLHS under hypothermic total circulatory arrest. We hypothesize that allopurinol may provide protection from cellular injury in this clinical context.
This report describes an unusual case of secondary nocturnal enuresis presumptively secondary to progressive bradycardia from complete heart block. Congenital complete heart block occurs in approximately 1 of 22,000 livebirths and is typically associated with structural congenital heart disease or maternal collagen vascular diseases. It can be entirely asymptomatic during infancy and childhood, depending in part on the escape rate and rhythm and other hemodynamic variables. The case described above was not diagnosed until the patient coincidentally underwent cardiac monitoring. The picture was confusing initially, as a tricyclic antidepressant medication had been ingested. Heart block is one of the known cardiovascular effects of tricyclic antidepressant overdose. However, the conduction disturbance should have resolved as the drug was excreted from the body. As children with congenital complete heart block get older, the ventricular escape rate typically decreases. In addition, as activity increases with age, more demand is placed for cardiac output. The resting end-diastolic volume is increased to elevate stroke volume in compensation for lower heart rate. As the escape rate decreases and the metabolic demand increases, patients with congenital complete heart block then may begin to develop symptoms. Typical symptoms in children include dizziness, Stokes-Adams syncopal attacks, fatigue, daytime somnolence, and other somatic complaints. Bedwetting has not been reported as an initial symptom, but in this case is likely secondary to the excessive somnolence and difficulty with arousal.(ABSTRACT TRUNCATED AT 250 WORDS)
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Since 1985, 354 neonates have undergone palliative reconstruction for hypoplastic left heart syndrome with 109 early deaths and 12 late deaths. Of the survivors, before 1989, 77 patients underwent a subsequent modified Fontan operation, consisting of baffling the atrial septal defect to the tricuspid valve (initial 25 patients) or intraatrial baffling of the inferior vena cava to the pulmonary arteries and superior vena cava (52 patients). There were 17 early deaths and three late deaths. Major serous effusions developed in 42 patients (54%) after Fontan operation. Since 1989, a staged approach to Fontan's operation was undertaken in an effort to reduce the volume load of the right ventricle as early as possible, to minimize the impact of rapid changes in ventricular geometry and diastolic function that can accompany a primary Fontan operation, and to reduce effusive complications. Thus, at a mean age of 6 months, 121 patients have undergone closure of aortopulmonary shunt, augmentation of central pulmonary arteries, and association of the superior vena cava with the branch pulmonary arteries (hemi-Fontan procedure). Of these, 61 patients have already undergone completion of the Fontan procedure with six early deaths and three late deaths. Major serous effusions developed in 28 patients (46%) with the staged Fontan. For perspective, the contemporary experience since January 1991 consists of 58 neonates who have undergone initial palliation with 11 deaths (19%), 17 patients who have undergone the hemi-Fontan procedure with one death (6%), and 21 patients who have undergone completion of the Fontan operation with one death (5%).(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: We reviewed the outcome of 76 consecutive patients (age range, 5 months to 6 years; median age, 19 months) who underwent a modified Fontan procedure after initial palliative surgery for hypoplastic left heart syndrome (HLHS) between January 1984 and December 1989. METHODS AND RESULTS: Modifications of the Fontan procedure included transatrial baffle of pulmonary venous return to the tricuspid valve (n = 10) or inferior vena cava baffle within the right atrium to the superior vena caval-pulmonary artery anastomosis, with pulmonary artery augmentation (n = 66). Actuarial survival rates were 74% (1 month), 58% (12 months), 56% (2 years), and 52% (4 years). Of the 43 survivors, 25 patients have returned for postoperative cardiac catheterization at a medium of 13 months after the Fontan procedure. Mean +/- SD hemodynamic values were cardiac index, 2.8 +/- 0.6 l/min/m2; right arterial pressure, 11 +/- 2 mm Hg; pulmonary artery wedge pressure, 6 +/- 3 mm Hg; and arterial oxygen saturation, 94 +/- 3%. No patient had significant tricuspid or native pulmonary valve insufficiency. CONCLUSIONS: Survival after the Fontan procedure in patients with HLHS is comparable to survival after a Fontan procedure in patients with other complex congenital heart lesions. In the subgroup of patients with HLHS who survived both reconstructive surgery and a Fontan procedure and have been evaluated by cardiac catheterization after a Fontan procedure, the use of the right ventricle as the systemic ventricle yielded excellent intermediate results for Fontan physiology.
OBJECTIVE: To compare a combination of epidural fentanyl and bupivacaine with bupivacaine alone for epidural analgesia in labour and to evaluate factors in addition to analgesia that may influence maternal satisfaction. DESIGN: A prospective randomised pilot study. SETTING: Birmingham Maternity Hospital. SUBJECTS: 85 primiparous women who requested epidural analgesia in labour and their babies. INTERVENTIONS: Group 1 mothers were treated with bupivacaine conventionally, group 2 mothers with bupivacaine and fentanyl in a more complex way designed to provide satisfactory analgesia but with less troublesome side effects. MAIN OUTCOME MEASURES: Overall maternal satisfaction, maternal perception of epidural analgesia and its side effects, and aspects of mothers' psychological states during labour, quantified using 100 mm visual linear analogue scales; the frequency of normal and operative deliveries; and measurements of neonatal wellbeing. RESULTS: Satisfaction was higher in group 2 mothers (median group difference +3 mm, 95% confidence interval +1 to +5, p = 0.012): this was associated with more normal deliveries (difference between proportions 0.23, 95% confidence interval +0.03 to +0.42); greater self control (median group difference -7 mm, -17 to -2, p = 0.003); and reduced unpleasantness of motor blockade (-10 mm, -19 to -5, p less than 0.001), sensory blockade (-5 mm, -11 to -2, p = 0.002) and shivering (-5 mm, -18 to 0, p = 0.046) at the expense of mild itching (0 mm, 0 to 0, p less than 0.001). Group 1 mothers found restricted movements more unpleasant (-1 mm, -11 to 0, p = 0.006) and were more sleepy (-4 mm, -20 to 0, p = 0.032). The addition of fentanyl to bupivacaine reduced the requirement for local anaesthetic (-33 mg, -55 to -15, p less than 0.001) without compromising analgesia. No adverse effects in neonates were attributed to the use of fentanyl. CONCLUSIONS: The already high maternal satisfaction from conventional epidural analgesia can be improved; epidural fentanyl may be combined with bupivacaine to reduce operative deliveries and confer other advantages that may increase maternal satisfaction. Further investigations should be performed to determine the exact mechanisms of these findings and, in particular, to develop a safe method of delivering such analgesia to women.
After undergoing initial reconstructive surgery for hypoplastic left heart syndrome performed between August 1985 and March 1989, 59 patients (age range 3 to 27 months, mean 13.8 +/- 4.5) underwent elective cardiac catheterization in anticipation of a modified Fontan procedure. Five important hemodynamic and anatomic features considered to be components of successful reconstructive surgery were specifically addressed. 1) Interatrial communication: Only two patients had a measured pressure difference of greater than 4 mm Hg across the atrial septum. 2) Tricuspid valve function: Angiography demonstrated significant tricuspid valve regurgitation in only five patients (moderate in two and severe in three). 3) Aortic arch: Pressure tracings from the right ventricle to the descending aorta revealed a gradient greater than 25 mm Hg in only two patients. 4) Pulmonary vasculature: Ten patients had a calculated pulmonary vascular resistance greater than 4 U.m2; 51 (86%) of the 59 patients had no evidence of distortion (stenosis or hypoplasia) of either the left or the right pulmonary artery. 5) Right ventricular function: Five patients had an end-diastolic pressure in the right ventricle greater than 12 mm Hg and two patients had qualitative assessment of decreased ventricular function. Comparison of catheterization data between survivors and nonsurvivors of the subsequent modified Fontan procedure showed that only significant tricuspid regurgitation is a possible predictor of poor outcome. After first stage reconstructive surgery for hypoplastic left heart syndrome, most survivors have favorable anatomy and hemodynamics at follow-up cardiac catheterization for a subsequent Fontan procedure.
Rats were placed in whole-body harness suspension in three configurations: antiorthostatic hypokinetic/hypodynamic suspension (AAH) to induce headward body fluid redistribution and unload the limbs, orthostatic hypokinetic/hypodynamic suspension (OHH) to unload the limbs without fluid redistribution, and harness restraint (HR) to produce the restraint stress of the model without fluid redistribution or musculoskeletal disuse. AHH and OHH suspension transiently increased interferon-gamma (IFN-gamma) production in response to the mitogen concanavalin A. Harness restraint alone did not affect IFN-gamma response. However, both suspension modeling and harness restraint caused a transient reduction in interleukin-1 (IL-1) and IL-2 responses to mitogen. This suggests that factors associated with musculoskeletal unloading affected IFN-gamma responses, while IL-1 and IL-2 responses were affected by the physiological stress of restraint.
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The use of Doppler color flow imaging and axial contrast angiography in the preoperative detection of additional ventricular septal defects (in the setting of a known large defect) were compared in a prospective fashion. One hundred seventy-nine infants with two ventricles (each of at least normal size) and a large, nonrestrictive ventricular septal defect underwent reparative surgery before 2 years of age. The reference standard for the presence of additional defects was intraoperative verification or (in cases in which the surgeon did not visualize any additional defect) subsequent identification at postoperative angiography, postoperative color Doppler examination or reoperation. Only six patients (3%) had additional ventricular septal defects confirmed at the time of repair; an additional five (3%) had defects found only postoperatively. The negative predictive value of Doppler color flow imaging and angiography was 0.95 (168 of 176) and 0.97 (168 of 174), respectively. The sensitivity was 0.27 (3 of 11) and 0.45 (5 of 11), respectively. For certain malformations with a very low prevalence of additional muscular defects (such as perimembranous ventricular septal defect with normally aligned great arteries), a clinical trial of reparative surgery without prior invasive study appears reasonable.
Between January 1987 and January 1989, all 129 patients (aged 11 days to 25 years, median 39 months) undergoing both an echocardiographic examination and cardiac catheterization after reparative surgery were prospectively included in a study to assess the accuracy of combined two-dimensional and Doppler color flow imaging. The patient diagnoses were transposition of the great arteries (n = 20), tetralogy of Fallot (n = 38), coarctation of the aorta (n = 24), complete atrioventricular (AV) canal (n = 15), atrial septal defect (n = 8), ventricular septal defects (n = 3), pulmonary stenosis (n = 4), aortic stenosis (n = 8) and subaortic stenosis (n = 9). In arterial tract stenosis, there was high correlation between Doppler estimates and catheterization-derived measurements of residual right ventricular outflow tract obstruction in patients after the arterial switch operation for transposition of the great arteries (r = 0.95) as well as in patients after corrective repair of tetralogy of Fallot (r = 0.84). In semilunar/AV valve regurgitation, graded as none, mild, moderate or severe, echocardiographic estimates correlated exactly with angiographic grading in 84% and differed by one angiographic grade in the other 16%. In residual left to right shunting, no hemodynamically significant shunt was missed by echocardiography. For residual shunts at the ventricular level (n = 32), addition of Doppler color flow imaging improved the sensitivity (from 63% to 94%) and the negative predictive value (from 88% to 98%). In elevated right ventricular pressure, Doppler-derived right ventricular-right atrial pressure estimates in 24 patients correlated well with catheterization measurements (r = 0.93). Combined two-dimensional and Doppler color flow echocardiography was highly accurate in the prospective evaluation of these four types of postoperative residual.
The outcome and clinical course before modified Fontan procedure were reviewed for 200 patients with hypoplastic left heart syndrome who underwent initial reconstructive surgery between August 1985 and March 1989. The median age at the time of initial reconstruction was 6 days (range, 1 day to 7.2 months). In 28 patients, a right modified Blalock-Taussig shunt was used; in 172 patients, a central shunt was placed. Additional procedures (n = 41) performed in 38 patients (median age, 5 months; range, 6 days to 17.5 months) were revision of systemic-to-pulmonary shunt (n = 15), arch reconstruction (n = 8), balloon angioplasty of arch obstruction (n = 7), atrial septectomy (n = 4), pulmonary artery angioplasty (n = 2), tricuspid valve annuloplasty or replacement (n = 4), and modified Glenn shunt (n = 1). There was no significant difference in the frequency of additional procedures performed more than 30 postoperative days in the survivors compared with the nonsurvivors. Actuarial survival rates were 0.66 (1 month), 0.48 (12 months), and 0.44 (18 months). Seventy percent of all deaths occurred during the initial admission, with 32% resulting from acute cardiovascular collapse during the first postoperative day. There was no statistical difference in actuarial survival when assessed by the type of shunt used or by anatomical subtype or when the influence of additional interventions was considered. Substantial improvement in outcome may be possible if immediate perioperative mortality can be reduced. We speculate that some of the intermediate mortality (30 days to 1 year) may be related to the effects of chronic exposure of the right ventricle to volume overload at systemic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
An uncommon but historically important form of transposition of the great arteries (S,D,D) was originally recognized in 1971. The unusual features of an aorta that is posterior and to the right of the pulmonary artery, a hypoplastic subaortic conus, and a well-developed subpulmonary conus influenced the evolution of the contemporary classification of conotruncal abnormalities and concepts of their development. Presented in this report is the case of a patient with transposition of the great arteries (S,D,D) and posterior aorta treated by an arterial switch operation. The unusual orientation of the great arteries did not preclude coronary transplantation or a satisfactory pulmonary arterial anastomosis. Moreover, the ventricular septal defect, which is characteristic of this atypical form of transposition of the great arteries, was most accessible for closure through the native aortic valve.
To determine whether preoperative demographic and metabolic variables correlated with early or late survival following palliative surgery for hypoplastic left heart syndrome, we reviewed the charts of 89 patients operated upon from October 1984 to January 1987. The variables analyzed were age at operation, lowest preoperative pH and H2CO3, highest preoperative arterial oxygen saturation, the occurrence of a preoperative cardiorespiratory arrest, and location of birth relative to the surgical institution. The data were evaluated by chi-squared, multivariate, and life-table analyses to the end of the first postoperative year. None of the factors analyzed significantly correlated with either short-term (less than or equal to 30 days) or long-term (greater than 30 days) survival. Thus, neither demographic nor metabolic factors including prior cardiorespiratory arrest should be considered contraindications to surgical palliation for hypoplastic left heart syndrome.
The arterial switch procedure has become an accepted reparative technique for transposition of the great arteries with or without ventricular septal defect. In this study the accuracy of prospective noninvasive imaging in detecting arterial tract obstruction and the prevalence and severity of arterial valvular regurgitation (as assessed by Doppler ultrasound) were evaluated in survivors of arterial repair. All 53 study patients underwent two-dimensional echocardiographic examination 2 days to 20 months (median 7 months) postoperatively; 43 patients also had pulsed and continuous wave Doppler studies. The accuracy of the noninvasive evaluation of arterial tract obstruction was determined by comparison of Doppler maximal instantaneous gradients with peak to peak gradients at nonsimultaneous catheterization in 26 patients. Twenty-one (81%) of the 26 patients underwent catheterization and successful pulsed and continuous wave Doppler examination of the right heart; 17 (81%) of these 21 had a maximal pressure gradient within 20 mm Hg of the peak to peak gradient obtained at catheterization. Echocardiographic identification of the stenotic site was correct in all eight of the patients in this group requiring reoperation. Twenty-three (88%) of the 26 patients who underwent catheterization had successful Doppler interrogation of the aortic tract; 22 (96%) of these 23 had a maximal instantaneous gradient within 20 mm Hg of the peak to peak catheterization gradient. Fourteen (32%) of 43 patients had mild or moderate pulmonary regurgitation by Doppler study. Three (7%) of the 43 had mild aortic regurgitation.
Thirty healthy patients, who were to undergo surgery which required tracheal intubation, were given an intravenous injection of enalaprilat (either 0.5 mg, 1 mg, 2 mg or 4 mg; six patients for each dose) or normal saline 17 minutes before induction of anaesthesia with thiopentone 3-5 mg/kg, and suxamethonium 1.5 mg/kg. Postural manoeuvres were performed 5 minutes before and 6, 11 and 16 minutes after enalaprilat or saline. Complete inhibition of angiotensin converting enzyme occurred with all doses of enalaprilat, which allowed the four different treatment groups to be considered as one large treated group. The mean arterial pressure was almost unchanged during the postural manoeuvres; the heart rate increased, mostly similarly (by approximately 10%) in both groups. Mean arterial pressure in the recumbent position decreased over the 17 minutes before induction in the enalaprilat group, and increased slightly in the control group (treated mean, -5.0%; controls mean, 1.8%; difference, -6.8%; 95% confidence intervals of difference, -2.3 to -11.3%, p less than 0.01). This difference was again seen after induction (treated, -8.0%; controls, 7.7%; confidence intervals of difference, -0.6 to -31%) and for a 5-minute period shortly after tracheal intubation. The increases in mean arterial pressure produced by intubation itself were similar in both groups (treated, + 36%; controls, + 35%; 95% confidence intervals of difference, -16% to + 18%). Changes in heart rate after induction were also similar in both groups. It is concluded that intravenous enalaprilat acted as a hypotensive agent with a sparing effect on autonomic reflexes, both before and after induction of anaesthesia.